Marcon L, Michaels F, Hattori N, Fargnoli K, Gallo R C, Franchini G
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
J Virol. 1991 Jul;65(7):3938-42. doi: 10.1128/JVI.65.7.3938-3942.1991.
Human immunodeficiency virus type 2 (HIV-2) is similar in genetic organization to HIV-1 but contains a unique gene (vpx) that encodes a 16-kDa protein. A replication-competent molecular clone of HIV-2 (HIV-2sbl/isy) that infects human primary cells in vitro and rhesus monkeys was used to generate three mutations in the vpx gene. In the first mutant, the vpx open reading frame was truncated at amino acid 20; the second mutant was tailored to eliminate the proline-rich carboxyl terminus of the protein; and the third mutant was obtained by addition of four amino acids (KDEL) to the carboxyl terminus of the protein to provide a retention signal in the endoplasmic reticulum. The viral infection kinetics of the three mutant viruses and isogeneic HIV-2sbl/isy in the SupT1 cell line were similar. Slight impairment in the early phases of viral replication was observed during infection of primary human peripheral blood mononuclear cells with the vpx mutant viruses. All of the vpx mutant viruses readily infected macrophages, indicating that vpx expression is dispensable for HIV-2 infection and replication in human macrophages.
2型人类免疫缺陷病毒(HIV-2)在基因结构上与HIV-1相似,但含有一个独特基因(vpx),该基因编码一种16千道尔顿的蛋白质。一种具有复制能力的HIV-2分子克隆(HIV-2sbl/isy),它能在体外感染人类原代细胞和恒河猴,被用于在vpx基因中产生三个突变。在第一个突变体中,vpx开放阅读框在第20个氨基酸处被截断;第二个突变体经设计以消除该蛋白质富含脯氨酸的羧基末端;第三个突变体是通过在该蛋白质的羧基末端添加四个氨基酸(KDEL)来在内质网中提供一个滞留信号而获得的。三种突变病毒和同基因的HIV-2sbl/isy在SupT1细胞系中的病毒感染动力学相似。在用vpx突变病毒感染原代人类外周血单核细胞的过程中,观察到病毒复制早期阶段有轻微损伤。所有vpx突变病毒都能轻易感染巨噬细胞,这表明vpx表达对于HIV-2在人类巨噬细胞中的感染和复制并非必需。